As both the brain and the tumor are complex systems, GBM cells are exposed to and manage to survive challenging environments with diverse dynamic stimuli. Those cells are highly diffusible and capable of resisting much of the treatments that we have introduced so far. With such abilities, it is reasonable to assume that GBM cells have an efficient adaptation process. In this project, we are interested to study the processes involved in this adaptation. We hypothesize that GBM adaptation actually includes two main processes: 1) a specific process that is stimulated by known, recurring stress inputs. This adaptation follows pre-evolved switches that were already developed during developmental stages or acquired epi/genetic changes in early cancer stages, coming from different types of GBM cells (Aim 1); and 2) a generic process that is stimulated by unforeseen stimuli: new switches that are formed based on a collective stochastic process of adaptation once a cell diffuses and faces unforeseen stimuli (Aim 2). These are two complementary processes that could be applicable to the outcome of targeted therapy with chemotherapy.